Loss or impairment of visual perception can result from a variety of causes. Examples include diseases that cause deterioration of the retina, such as Retinitis Pigmentosa, which affects over one million people worldwide, and can lead to profound blindness. Other such diseases include Usher syndrome, age-related macular degeneration, Stargardt macular dystrophy, Leber congenital amaurosis and Bardet-Biedl syndrome.
There is currently no clinical means of restoring visual perception to patients who have developed blindness (no light perception) as a result of Retinitis Pigmentosa or other inherited or acquired retinal dystrophies. There is also no clinical means of preventing the deterioration towards blindness that occurs in the retinal dystrophies, (Sharma R K, & Ehinger B. Management of hereditary retinal degenerations: present status and future directions. Survey of Ophthalmology 1999; 43(5):427-44.; Chong N H, & Bird A C. Management of inherited outer retinal dystrophies: present and future. British Journal of Ophthalmology 1999; 83(1):120-2).
Experimental treatments such as gene therapy, neural cell transplantation, growth factors, vitamin supplementation, antioxidants and regulators of apoptosis have shown no success in restoring visual sensations to blind patients in clinical trials (Sharma & Ehinger, 1999, above). It is unlikely that any of these methods will be able to restore visual perceptions to blind patients in the medium term (5-10 years), if at all (Chong & Bird, 1999, above). This is due to the poor capacity of neural tissue, such as that in the retina, for repair and regeneration (Mitchell R N, & Cotran R S. Chapter 3: Repair: Cell Regeneration, Fibrosis, and Wound Healing. In: Kumar V, Cotran R S, Robbins S L, eds. Basic Pathology. 6 ed. Philadelphia: W. B. Saunders, 1997). Therefore an approach to restoring vision based on bypassing the damaged elements of the visual pathway is required (Scarlatis G. Optical prosthesis: visions of the future. JAMA 2000; 283(17):2297.; Larkin M. Artificial-vision research comes into focus. Lancet 2000; 355(9209):1080).
The only experimental method that has successfully restored visual perceptions to irreversibly blind patients is electrical stimulation of the eye, optic nerve or brain with implanted electrodes (Veraart et al. 1998, above; Maynard E M. Visual prostheses. Annual Review of Biomedical Engineering 2001; 3:145-68; Brindley G S, & Lewin W S. The sensations produced by electrical stimulation of the visual cortex. Journal of Physiology 1968; 196(2):479-93; Humayun et al. Visual perception elicited by electrical stimulation of retina in blind humans. Archives of Ophthalmology 1996; 114(1):40-6). Of these three approaches, electrical stimulation of the visual cortex is also the only approach to developing a bionic eye so far that has restored visual perceptions that are able to increase a blind patient's mobility and independence (Dobelle W H. Artificial vision for the blind by connecting a television camera to the visual cortex. ASAIO Journal 2000; 46(1):3-9).
Electrical currents can have many effects on the eye. One such effect is a therapeutic effect, whereby electrical current can help to heal cells and tissues that have been damaged by disease and therefore improve vision. Electrical current can also be used to activate surviving nervous cells in the eye that have lost their natural input due to a disease process. By activating these surviving cells, signals are relayed to brain which cause a patient to perceive a visual sensation, and such electrically evoked, artificially induced visual phenomena are called “phosphenes”. This is generally known as a prosthetically induced visual effect.
The use of electricity in a therapeutic capacity to heal tissues in the eye has been suggested by a number of researchers: for example, in 1989, Shandurina and colleagues working at the Academy of Medical Sciences in Russia, reported successful results from therapeutic electrical stimulation of the optic nerve in patients with visual impairment. In 2003, Chow, et al. (Chow et al. Subretinal Artificial Silicon Retina Microchip Implantation in Retinitis Pigmentosa Patients: Long Term Follow-Up. ARVO Meeting Abstracts 2003; 44(5):4205) reported that electrical stimulation from a device that they had implanted intraocularly near the retina of patient's eyes was improving the subjects vision by having a neurotrophic effect on the diseased retinal tissues. U.S. Pat. No. 5,147,284, to Federov, describes a device consisting of two electrodes, one placed on the optic nerve and one placed on the sclera, for the treatment of visual disorders such as optic atrophy through electrical stimulation.
Other approaches to improve visual perception using electrical stimulation include placement of a device which has photosensitive components and electrodes at a “subretinal location” at the outer aspect of the neuroretina. Examples of such devices are described in U.S. Pat. No. 2,760,483 to Tassicker, U.S. Pat. No. 5,016,633 to Chow and U.S. Pat. No. 6,347,250, to Nisch.
Another approach is to place electrodes at an “epiretinal” location on the surface of the retina, between the retina and the vitreous. Such approaches are described in U.S. Pat. No. 5,109,844, to De Juan, and U.S. Pat. No. 6,324,429, to Shire.
Another approach is to implant electrodes to electrically stimulate the optic nerve. This is described, for example, in U.S. Pat. No. 6,442,431, to Veraart.
Devices have also been proposed for direct electrical stimulation of the visual region of the brain, by using electrical stimulation of the visual system to elicit phosphene perception. There have been a number of different approaches to the design of a device for this purpose, described for example in U.S. Pat. No. 5,215,088 to Normann, which discusses penetrating electrodes for implantation into the tissues of the brain.
It is surprising that despite an intensive research effort by a number of well-funded groups over the past 10 years aimed at developing a visual prosthesis with intraocular electrodes placed at an epiretinal, (Humayun et al. 1996 above; Grumet et al., Multi-electrode stimulation and recording in the isolated retina Journal of Neuroscience Methods 2000; 101(1):31-42; Humayun M S. Intraocular retinal prosthesis. Transactions of the American Ophthalmological Society 2001; 99:271-300; de Juan et al. Pattern electrical stimulation of the human retina. Vision Research 1999; 39(15):2569-76,) or subretinal, (Chow A Y & Chow V Y. Subretinal electrical stimulation of the rabbit retina. Neuroscience Letters 1997; 225(1):13-6.; Stett et al., Electrical multisite stimulation of the isolated chicken retina. Vision Research 2000; 40(13):1785-95) location, electrical stimulation of the retina has not met with the success of visual cortex stimulation (Rizzo et al. Retinal prosthesis: an encouraging first decade with major challenges ahead. Ophthalmology 2001; 108(1):13-4). This is because there are significant problems to be overcome at the electrode-tissue interface before an intraocular retina-based bionic implant can be considered a viable approach to treating blindness (Rizzo J F, Wyatt J, Humayun M, et al., above; Margalit, et al. Retinal prosthesis for the blind. Survey of Ophthalmology 2002; 47(4):335-56).
Currently there are two chronic trials of intraocular retinal implants occurring. In a study of subretinal stimulation by Chow et al, improvements in the visual acuity of implanted patients could not be explained by a neuroprosthetic effect of the implanted device, and the investigators have suggested that low level electrical stimulation of the retina is having a yet undefined “neurotrophic effect” (Chow et al. 2003, above). Regardless of whether this hypothesis is verified, these devices are not acting as conventional neural prostheses (Chapin J K & Moxon K A. Neural prostheses for restoration of sensory and motor function. Boca Raton: CRC Press, 2001), and are instead using electrical stimulation for a therapeutic effect.
In the other study by Humayun et el. (Humayun et al. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vision Res 2003; 43(24):2573-81.), a 4×4 array of 16 platinum disc electrodes, each of 520 μm diameter, with an inter-electrode centre-to-centre spacing of 720 μm was implanted with a tack at the epiretinal surface of a blind human patient. A cable from the electrode array passed through the sclera and tracked subcutaneously to a stimulator outside the orbit. Electrical stimulation of this array elicited the subjective perception of small spots of light in the patient's visual field. Interfacing the device with a camera allowed the patient to detect the presence of light and large objects (Humayun et el. 2003, above).
Hence, the devices and approaches of the prior art involve invasive stimulation of the visual system, and in particular, the eye and optic nerve, of patients suffering visual impairments. There thus remains a need for new approaches for enhancing or restoring visual perception in patients, or preventing deterioration of visual perception in patients, that do not require such invasive and potentially dangerous surgery.